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AS160 (human)

Overview AS160 a widely-expressed Rab GTPase-activating protein which apparently plays a role in mediating insulin action. Phosphorylated by the Ser/Thr protein kinase Akt in response to insulin. Is redistributed from low-density microsomes to the cytosol upon insulin treatment. Insulin stimulation of GLUT4 exocytosis is dependent on AS160. The translocation of GLUT4 from intracellular storage sites to the cell surface functions to stimulate insulin uptake by adipose and muscle tissue. Its expression is decreased by twofold in pancreatic islets in type 2 diabetes patients compared to control subjects; its phosphorylation is impaired in skeletal muscle of type 2 diabetics. The protein is expressed in pancreatic Langerhans islets, including beta cells. Up-regulated in T cells from patients with atopic dermatitis. Two alternatively spliced isoforms have been described. Isoform 2, which promotes GLUT4 translocation at the plasma membrane, is the highest overexpressed in most tissues. Isoform 2 shows a cytoplasmic perinuclear localization in a myoblastic cell line in resting and insulin-stimulated cells Isoform 2 is strongly expressed in adrenal and thyroid gland, and also in lung, kidney, colon, brain and adipose tissue. Isoform 2 is moderately expressed in skeletal muscle. Isoform 1 is highly expressed in skeletal muscle and heart, but was not detectable in the liver or adipose tissue. Note: This description may include information from UniProtKB. Protein type: GTPase activating protein, Rab Cellular Component: cytoplasm Molecular Function: Rab GTPase activator activity Biological Process: vesicle-mediated transport; cellular response to insulin stimulus Reference #:  O60343 (UniProtKB) Alt. Names/Synonyms: Acrg embryonic lethality minimal region ortholog; Akt substrate of 160 kDa; AS160; DKFZp779C0666; KIAA0603; TBC (Tre-2, BUB2, CDC16) domain-containing protein; TBC1 domain family member 4; TBC1 domain family, member 4; TBC1D4; TBCD4 Gene Symbols: TBC1D4 Molecular weight: 146,563 Da Basal Isoelectric point: 6.57  Predict pI for various phosphorylation states CST Pathways:  Insulin Receptor Signaling  |  PI3K/Akt Signaling Protein-Specific Antibodies or siRNAs from Cell Signaling Technology®

Select Structure to View Below AS160 3QYB - A=874-1170 (human)

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	Sites Implicated In
molecular association, regulation: S318‑p, S341‑p, T568‑p, S588‑p, T642‑p, S751‑p

	Modification Sites and Domains	Show Modification Legend
Click here to view phosphorylation modifications only

	Modification Sites in Parent Protein, Orthologs, and Isoforms	Show Modification Legend

SS  SS: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.	MS  MS: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.			human ► Hide Isoforms
0	1		S66-p	MAEIRRRsQKPEAGG
0	2		V259	LADLEVVVPGsPGDC
0	16		S262-p	LEVVVPGsPGDCLPE
0	1		D272-ca	DCLPEEAdGtDTHLG
0	1		T274-p	LPEEAdGtDTHLGLP
0	1		-	gap
0	3		S285-p	LGLPAGAsQPALTSS
0	2		S304-p	PERILEDsGFDEQQE
0	2		S314-p	DEQQEFRsRCssVtG
0	5		S317-p	QEFRsRCssVtGVQR
7	318		S318-p	EFRsRCssVtGVQRR
0	8		T320-p	RsRCssVtGVQRRVH
6	312		S341-p	QPRRRHAsAPsHVQP
0	20		S344-p	RRHAsAPsHVQPsDs
0	6		S349-p	APsHVQPsDsEKNRt
0	1		S351-p	sHVQPsDsEKNRtML
0	1		T356-p	sDsEKNRtMLFQVGR
0	2		S370-p	RFEINLIsPDTKSVV
0	1		K477-a	GLYPPRAkLVIQRHL
0	3		S485-p	LVIQRHLsSLTDNEQ
0	1		T528	LCEAKQKTHVHIGEG
0	1		S540	GEGPSTISNSTIPEN
0	1		S551-p	IPENATSsGRFKLDI
0	30		S566-p	LKNKAKRsLtssLEN
2	18		T568-p	NKAKRsLtssLENIF
0	9		S569-p	KAKRsLtssLENIFS
3	86		S570-p	AKRsLtssLENIFSR
9	224		S588-p	RMRGRLGsVDsFERS
0	32		S591-p	GRLGsVDsFERSNsL
0	12		S597-p	DsFERSNsLAsEKDY
0	8		S600-p	ERSNsLAsEKDYSPG
0	2		S605	LAsEKDYSPGDsPPG
0	10		S609-p	KDYSPGDsPPGtPPA
0	6		T613-p	PGDsPPGtPPAsPPS
0	5		S617-p	PPGtPPAsPPSsAWQ
0	1		S620	tPPAsPPSsAWQTFP
0	1		S621-p	PPAsPPSsAWQTFPE
0	1		S633-p	FPEEDSDsPQFRRRA
20	126		T642-p	QFRRRAHtFsHPPss
0	14		S644-p	RRRAHtFsHPPssTK
0	4		S648-p	HtFsHPPssTKRKLN
0	5		S649-p	tFsHPPssTKRKLNL
3	40		S666-p	GRAQGVRsPLLRQSS
0	32		S672	RsPLLRQSSSEQCSN
0	43		S673	sPLLRQSSSEQCSNL
0	15		S674	PLLRQSSSEQCSNLS
0	30		S678	QSSSEQCSNLSSVRR
1	1		S704-p	PSLHTSFsAPSFTAP
0	28		T749-p	DGEGRKRtsstCsNE
0	41		S750-p	GEGRKRtsstCsNEs
7	52		S751-p	EGRKRtsstCsNEsL
0	51		T752-p	GRKRtsstCsNEsLs
0	123		S754-p	KRtsstCsNEsLsVG
0	76		S757-p	sstCsNEsLsVGGtS
0	12		S759-p	tCsNEsLsVGGtSVt
0	3		T763-p	EsLsVGGtSVtPRRI
0	14		T766-p	sVGGtSVtPRRISWR
0	2		S782-p	RIFLRVAsPMNKsPS
0	2		S787-p	VAsPMNKsPSAMQQQ
0	1		S1126	VALSLLSSQETLIME
0	2		Y1191-p	DELQESSySCEDSET

	AS160 iso3
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
-	gap
T40	LCEAKQKTHVHIGEG
S52	GEGPSTISNSTIPEN
S63	IPENATSSGRFKLDI
S78	LKNKAKRSLtSsLEN
T80-p	NKAKRSLtSsLENIF
S81	KAKRSLtSsLENIFS
S82-p	AKRSLtSsLENIFSR
S100-p	RMRGRLGsVDSFERS
S103	GRLGsVDSFERSNSL
S109	DSFERSNSLASEKDY
S112	ERSNSLASEKDYSPG
S117	LASEKDYSPGDSPPG
S121	KDYSPGDSPPGTPPA
T125	PGDSPPGTPPASPPS
S129	PPGTPPASPPSSAWQ
S132	TPPASPPSSAWQTFP
S133	PPASPPSSAWQTFPE
S145	FPEEDSDSPQFRRRA
T154-p	QFRRRAHtFsHPPSS
S156-p	RRRAHtFsHPPSSTK
S160	HtFsHPPSSTKRKLN
S161	tFsHPPSSTKRKLNL
S178-p	GRAQGVRsPLLRQss
S184-p	RsPLLRQsssEQCsD
S185-p	sPLLRQsssEQCsDG
S186-p	PLLRQsssEQCsDGE
S190-p	QsssEQCsDGEGRKR
-	gap
T198-p	DGEGRKRtsstCsNE
S199-p	GEGRKRtsstCsNEs
S200-p	EGRKRtsstCsNEsL
T201-p	GRKRtsstCsNEsLs
S203-p	KRtsstCsNEsLsVG
S206-p	sstCsNEsLsVGGTS
S208-p	tCsNEsLsVGGTSVt
T212	EsLsVGGTSVtPRRI
T215-p	sVGGTSVtPRRISWR
S231	RIFLRVASPMNKSPS
S236	VASPMNKSPSAMQQQ
-	gap
-	gap

	mouse ► Hide Isoforms
S66	MAEIRRRSQKPDAGG
S258-p	MGVLEVEsPVsPDDS
S261-p	LEVEsPVsPDDSLPE
D271	DSLPEKADGTVNsPR
T273	LPEKADGTVNsPRAL
S276-p	KADGTVNsPRALPSL
S291	ASLPALASQPALASS
C310	PERILEDCGFDEQQE
S320-p	DEQQEFRsRCssVTG
S323-p	QEFRsRCssVTGVMQ
S324-p	EFRsRCssVTGVMQK
T326	RsRCssVTGVMQKKV
S348-p	QPRRRHAsAPsHVQP
S351-p	RRHAsAPsHVQPSDS
S356	APsHVQPSDSEKNRT
S358	sHVQPSDSEKNRTML
T363	SDSEKNRTMLFQVGR
S377-p	RFEINLIsPDTKSVV
K484	GLYPPRAKLVIQRHL
S492-p	LVIQRHLsSLTDNEQ
T535	LCEAKQRTHVHIGEG
S547	GEGPAIISNSTIPEN
G558	IPENVTSGGRFKLDV
S573-p	LKNKAKRsLtssLEN
T575-p	NKAKRsLtssLENIF
S576-p	KAKRsLtssLENIFS
S577-p	AKRsLtssLENIFSR
S595-p	RMRGRLGsMDsFERA
S598-p	GRLGsMDsFERANsL
S604-p	DsFERANsLASEKDF
S607	ERANsLASEKDFsPG
S612-p	LASEKDFsPGDsPPG
S616-p	KDFsPGDsPPGtPPA
T620-p	PGDsPPGtPPAsPLs
S624-p	PPGtPPAsPLsSAWH
S627-p	tPPAsPLsSAWHAFP
S628	PPAsPLsSAWHAFPE
S640-p	FPEEDSDsPQFRRRA
T649-p	QFRRRAHtFsHPPSS
S651-p	RRRAHtFsHPPSSSR
S655	HtFsHPPSSSRRKLN
S656	tFsHPPSSSRRKLNL
S673-p	GKAHGLRsPLLRQSs
S679	RsPLLRQSsSEQCSI
S680-p	sPLLRQSsSEQCSIV
S681	PLLRQSsSEQCSIVP
S685	QSsSEQCSIVPSARR
S711-p	PSLHTSFsAPSFTAP
T756-p	DGEGRKRtsstCsNE
S757-p	GEGRKRtsstCsNEs
S758-p	EGRKRtsstCsNEsL
T759-p	GRKRtsstCsNEsLN
S761-p	KRtsstCsNEsLNAG
S764-p	sstCsNEsLNAGGtP
N766	tCsNEsLNAGGtPVt
T770-p	EsLNAGGtPVtPRRV
T773-p	NAGGtPVtPRRVSWR
S789-p	RIFLRVAsPVNKsPS
S794-p	VAsPVNKsPSAMQQQ
S1135-p	VALSLLSsQEALIME
Y1200	DELLESSYACEDNES

	AS160 iso2
S66	MAEIRRRSQKPDAGG
S258	MGVLEVESPVSPDDS
S261	LEVESPVSPDDSLPE
D271	DSLPEKADGTVNSPR
T273	LPEKADGTVNSPRAL
S276	KADGTVNSPRALPSL
S291	ASLPALASQPALASS
C310	PERILEDCGFDEQQE
S320	DEQQEFRSRCSSVTG
S323	QEFRSRCSSVTGVMQ
S324	EFRSRCSSVTGVMQK
T326	RSRCSSVTGVMQKKV
S348	QPRRRHASAPSHVQP
S351	RRHASAPSHVQPSDS
S356	APSHVQPSDSEKNRT
S358	SHVQPSDSEKNRTML
T363	SDSEKNRTMLFQVGR
S377	RFEINLISPDTKSVV
K484	GLYPPRAKLVIQRHL
S492	LVIQRHLSSLTDNEQ
T535	LCEAKQRTHVHIGEG
S547	GEGPAIISNSTIPEN
G558	IPENVTSGGRFKLDV
S573	LKNKAKRSLTSSLEN
T575	NKAKRSLTSSLENIF
S576	KAKRSLTSSLENIFS
S577	AKRSLTSSLENIFSR
S595	RMRGRLGSMDSFERA
S598	GRLGSMDSFERANSL
S604	DSFERANSLASEKDF
S607	ERANSLASEKDFSPG
S612	LASEKDFSPGDSPPG
S616	KDFSPGDSPPGTPPA
T620	PGDSPPGTPPASPLS
S624	PPGTPPASPLSSAWH
S627	TPPASPLSSAWHAFP
S628	PPASPLSSAWHAFPE
S640	FPEEDSDSPQFRRRA
T649	QFRRRAHTFSHPPSS
S651	RRRAHTFSHPPSSSR
S655	HTFSHPPSSSRRKLN
S656	TFSHPPSSSRRKLNL
S673-p	GKAHGLRsPLLRQss
S679-p	RsPLLRQsssEQCsD
S680-p	sPLLRQsssEQCsDG
S681-p	PLLRQsssEQCsDGE
S685-p	QsssEQCsDGEGRKR
-	gap
T693	DGEGRKRTSSTCSNE
S694	GEGRKRTSSTCSNES
S695	EGRKRTSSTCSNESL
T696	GRKRTSSTCSNESLN
S698	KRTSSTCSNESLNAG
S701	SSTCSNESLNAGGTP
N703	TCSNESLNAGGTPVT
T707	ESLNAGGTPVTPRRV
T710	NAGGTPVTPRRVSWR
S726	RIFLRVASPVNKSPS
S731	VASPVNKSPSAMQQQ
-	gap
-	gap

	rat
S66	MAEIRRRSLKPEAGG
S260	MGVLEAESPVSPDDG
S263	LEAESPVSPDDGLPE
D273	DGLPEKPDGLVNCPR
L275	LPEKPDGLVNCPRAL
C278	KPDGLVNCPRALPSL
S293	ASLPALASQPALASS
C312	PERILEDCGFDEQQE
S322	DEQQEFRSRCSSVTG
S325	QEFRSRCSSVTGVMQ
S326	EFRSRCSSVTGVMQK
T328	RSRCSSVTGVMQKKV
S350-p	QPRRRHAsAPSHVQP
S353	RRHAsAPSHVQPSDS
S358	APSHVQPSDSEKNRT
S360	SHVQPSDSEKNRTML
T365	SDSEKNRTMLFQVGR
S379	RFEINLISPDTKSVV
K486	GLYPPRAKLVIQRHL
S494	LVIQRHLSSLTDNEQ
T537-p	LCEAKQKtHVHIGEG
S549-p	GEGQAIIsNSTIPEN
G560	IPENSTSGGRFKLDV
S575	LKNKAKRSLTSSLEN
T577	NKAKRSLTSSLENIF
S578	KAKRSLTSSLENIFS
S579	AKRSLTSSLENIFSR
S597	RMRGRLGSVDSFERS
S600	GRLGSVDSFERSNSL
S606	DSFERSNSLASEKDF
S609	ERSNSLASEKDFSPG
S614	LASEKDFSPGGSPPG
S618	KDFSPGGSPPGTPPA
T622	PGGSPPGTPPASPLS
S626	PPGTPPASPLSSAWH
S629	TPPASPLSSAWHTFP
S630	PPASPLSSAWHTFPE
S642	FPEEDSDSPQFRRRA
T651-p	QFRRRAHtFSHPPSS
S653	RRRAHtFSHPPSSSR
S657	HtFSHPPSSSRRKLN
S658	tFSHPPSSSRRKLNL
S675	GKAHGLRSPLLRQNS
N681	RSPLLRQNSSEQCSV
S682	SPLLRQNSSEQCSVL
S683	PLLRQNSSEQCSVLP
S687	QNSSEQCSVLPSARR
S713	PSLHTSFSAPSFTAS
T758	DGEGRKRTSSTCSNE
S759	GEGRKRTSSTCSNES
S760	EGRKRTSSTCSNESL
T761	GRKRTSSTCSNESLS
S763	KRTSSTCSNESLSAG
S766	SSTCSNESLSAGGTP
S768	TCSNESLSAGGTPVT
T772	ESLSAGGTPVTPRRI
T775	SAGGTPVTPRRISWR
S791	RIFLRVASPVNKSPS
S796	VASPVNKSPSAMQQQ
S1137	VALSLLSSQEALVME
Y1202	DELLESSYACEDNES

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